The objective of this COBRE renewal application is to continue to develop the research careers of promising junior investigators In Cancer Genetics and to build core Programmatic strength in this area. Career development will utilize a strong core of research mentors who will provide career development advice as well as sound practical advice on scientific development and lab management. The five projects in this COBRE focus one several overlapping themes that contribute to our understanding of genetic instability, cellular inflammation, and the cell's responses to these factors. All but one of the proposals specifically focus on mouse models for studying cancer, and all projects have a high translational relevance. An internal advisory committee composed of mentors and core directors for this COBRE are all strongly committed to the program, and have outstanding research and mentoring records. In addition, a prominent board of external advisors with outstanding research careers and track records of career development for junior scientists will participate in both the guidance and evaluation of the progress of the junior investigators and the COBRE program itself. Career development will involve a series of program meetings, exposure to didactic grant-writing sessions, and seminars to develop a highly collaborative environment for both the junior faculty, as well as other members of the Louisiana Cancer Research Consortium (LCRC). The COBRE also provides outstanding core facility development for our scientists to make new experiments available to them. The LCRC provides an outstanding interdisiplinary and interinstitutional environment for cancer research involving Tulane Univerisy, LSU Heath Sciences Center and Xavier University. The LCRC is funded by a long-term state tobacco tax with the express goal of competing for NCI designation as a cancer center in New Orleans. The LCRC provides outstanding recruitment in the next few years, a new building dedicated to the LCRC and a series of well-operated core facilities. This COBRE represents the centerpiece of the LCRC and contributed strongly to our rebuilding post-Katrina as well as providing the framework that helps guide mentoring and development throughout the LCRC.